Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002539634 | SCV003305393 | uncertain significance | Autosomal recessive polycystic kidney disease | 2022-08-15 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 2840 of the PKHD1 protein (p.Arg2840His). This variant is present in population databases (rs373643848, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1255561). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PKHD1 protein function. This variant disrupts the p.Arg2840 amino acid residue in PKHD1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15805161, 30507656). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Laboratory of Gastroenterology and Hepatology, |
RCV001844890 | SCV001877016 | likely benign | Autosomal dominant polycystic kidney disease | 2021-09-01 | no assertion criteria provided | research |